Devices for trapping and controlling microparticles with radiation

ABSTRACT

A particle manipulation device includes a substrate and a microchannel included in the substrate and configured to receive a fluid including particles therein. A biasing structure is formed on the substrate adjacent to, but outside the microchannel. The biasing structure is configured to dispense radiation at a frequency to bias movement of the particles within the microchannel from outside the microchannel.

BACKGROUND

Technical Field

The present invention relates to particle manipulation devices, and moreparticularly to devices having paths and mechanisms for trapping andcontrolling microparticles and microorganisms as well as radiationgenerating electronic circuits for biasing of the microparticles.

Description of the Related Art

Point of Care (PoC) devices have increased in the interest formicrofluidics-based devices. Microfluidics-based devices have thepotential to perform entire biological experiments or immunologicaltests on a single credit card-sized or even smaller chip. PoC devicesprovide miniaturized laboratories for fast, inexpensive, easy to use,portable tests, such as e.g., blood sugar testing and the like.

Techniques exploiting dielectrophoretic (DEP) forces have emerged as apowerful touch-less method for cell and particle discrimination,separation, isolation or concentration, useful for sample processing.The dielectrophoretic (DEP) forces arise from interactions offield-induced charge polarization in cells or particles with fieldinhomogeneneity that acts to attract (or repel) cells to (or from)electric field maxima for positive (or negative) dielectrophoresisforces. An electrically polarizable object will be trapped in a regionof a focused electric field. These forces depend not only on thegeometrical configuration and excitation scheme of the electrode arraybut also on the dielectric properties of the cell or particle and of itssuspending medium. The magnitude, direction and frequency dependenciesof DEP responses depend on the composition, size and conductivity ofboth particle and medium.

DEP has been employed for the separation of live from dead yeast cells,live from dead bacteria cells, malaria-infected cells from healthycells, and human leukemia cells from healthy blood cells. For example,the membrane of red blood cells (erythrocytes) turn very permeable toions when they become infected by malarial parasites, resulting in theloss of internal ions to the low-conductivity suspending medium and amuch lower internal conductivity as compared to healthy red blood cells.

One way to make a DEP trap is to create an electric field gradient withan arrangement of planar metallic electrodes in a channel. A form ofelectrode-less dielectrophoresis manipulation can be done through theuse of a strongly focused beam of light, commonly known as “opticaltweezers” or through a hybrid variation using photoconductive materials,the “optoelectronic tweezers”. Intensity gradients in the convergingbeam draw small objects, such as a colloidal particle toward the focus,such that particles can be trapped in three dimensions near the focalpoint. They can operate by dynamically positioning potential energyminima and maxima.

While electrodeless DEP does not need metal evaporation during thefabrication, the structure is chemically inert with no impact on cellintegrity or viability, and it avoids electrolysis at metal DEPelectrodes with very high electric fields; this approach requires large,expensive, energy-intensive equipment that is external to the microchipand can only be used in a laboratory setting. Other electrode-less DEPstructures involve changes in the microfluidic channel geometry such asconstrictions or pillars.

SUMMARY

A particle manipulation device includes a substrate and a microchannelincluded in the substrate and configured to receive a fluid includingparticles therein. A biasing structure is formed on the substrateadjacent to, but outside the microchannel. The biasing structure isconfigured to dispense radiation at a frequency to bias movement of theparticles within the microchannel from outside the microchannel.

Another particle manipulation device includes a chip including asubstrate, a microchannel included in the substrate and configured toreceive a fluid including particles therein; and at least one biasingstructure formed on the substrate adjacent to but outside themicrochannel. The at least one biasing structure is configured todispense radiation at a frequency to bias movement of the particleswithin the microchannel from outside the microchannel. A control moduleincludes a generation circuit configured to generate a signal forexciting the biasing structures.

A method for particle manipulation includes introducing a fluid havingparticles therein to a microchannel included in a substrate andconfigured to receive the fluid having the particles therein and biasingthe particles traveling in the microchannel using at least one biasingstructure formed on the substrate adjacent to but outside themicrochannel, the at least one biasing structure being configured todispense radiation at a frequency to bias movement of the particleswithin the microchannel from outside the microchannel.

These and other features and advantages will become apparent from thefollowing detailed description of illustrative embodiments thereof,which is to be read in connection with the accompanying drawings.

BRIEF DESCRIPTION OF DRAWINGS

The disclosure will provide details in the following description ofpreferred embodiments with reference to the following figures wherein:

FIG. 1A is a top view of a particle manipulation device including amicrochannel and electronic biasing structures on a same substrate orchip in accordance with the present principles;

FIG. 1B is a side view of the particle manipulation device of FIG. 1Aincluding a ground plane and other layers on the substrate or chip inaccordance with the present principles;

FIG. 2 is a perspective view of a particle manipulation device connectedto a mobile device with an integrated image sensor, such as a smartphone, to view images, receive optical feedback and provide controlsignals for controlling biasing structures in accordance with thepresent principles;

FIG. 3 shows top views of a particle manipulation device after two timeperiods showing a trapping operation followed by a rinsing operation inaccordance with the present principles;

FIG. 4 is a top view of a particle manipulation device showing amultipath microchannel with electronic biasing structures for separatingparticles in accordance with the present principles;

FIG. 5 is a top view of a particle manipulation device having a sensorand detection chamber in accordance with the present principles;

FIG. 6 is a top view of a particle manipulation device connected to anexternal control and data processing system or device, referred to as areader, in accordance with the present principles;

FIG. 7 is a top view of a particle manipulation device in combinationwith the reader elements fabricated as a monolithic structure on a chipor substrate in accordance with the present principles; and

FIG. 8 is a block/flow diagram showing a particle manipulation processin accordance with illustrative embodiments.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

In accordance with the present principles, devices and methods aredescribed that eliminate the need for large, expensive andenergy-intensive equipment for generating a focused beam of light in“optical tweezers” settings. In particularly useful embodiments, byincorporating electromagnetic radiating elements on a surface of amicrofluidic chip, external to microchannel cavities, the challengesassociated with in-situ electrodes in direct contact with the fluid areavoided. Microstrip patch antennas can be employed as inexpensiveelectromagnetic radiating elements and can be implemented on a surfaceof the chip with a ground plane on a bottom surface of a substrate ofthe chip, and a coaxial feeding line on a side of the chip or throughthe substrate.

In other embodiments, an antenna configuration and radiation pattern canbe designed and optimized to perform any of the trapping, separation orconcentration of micro-particles or cells through dielectrophoresis(DEP). Antenna arrays with phased feeds can be employed to furtheroptimize and enhance directivity of the radiation beam, or to permitreal-time beam steering through control circuitry and semi-independentfeeding of antennas. This provides flexibility to change the DEPfunctionality in real-time and provides a less expensive alternative tooptical tweezers, even for disposable devices in Point of Care (PoC)applications.

Additional elements for focusing or guiding of electromagnetic waves mayinclude electromagnetic band-gap structures, metamaterial components orsurface plasmons inducing elements, which can also be incorporated intothe chip. The electromagnetic radiation element (antenna) can also beimplemented externally to the microfluidic chip, as part of areader/controlling circuitry that is not necessarily in direct contactwith the chip substrate. In-situ electrodes inside micro-channel canstill also be employed for more advanced functionality.

The present principles may incorporate an in-situ image sensor arraycomponent (CMOS or CCD based), which can be either integrated into thedevice or integrated as part of an external reader and/or controllingcircuitry, to capture real time images of the flow through themicro-channels. This image sensor can be connected with an imageprocessing element that determines the status of the fluid flow in thechannel and determines the proper feedback signal to be applied on theantenna feeding line that produces the optimum radiation pattern througha feedback control loop for real-time particle manipulation. The imagesensor and image processing element can be used for detection or moreaccurate and precise diagnostic purposes. For example, malariaparasitized cell sorting and concentration through electromagnetic-basedDEP and image capture and identification with image pattern recognitionsoftware.

Light waves are a form of high frequency electromagnetic wave carryingelectric and magnetic energy through space. Lower frequencyelectromagnetic radiation can be generated through antennas which areelectrical devices that convert electric power into electromagneticwaves in the radio, microwave and millimeter wave range (wavelengthsdown to 0.1 mm for THz radiation). Many structures, designs, materialsand antenna sizes may be employed in accordance with the presentprinciples. Antenna arrays enable higher directivity and steeringcapability of the radiation pattern. After particles or cells areprocessed (separated, concentrated, isolated, etc.) through DEP biasingmethods, detection/recognition or diagnosis can employ other physicalmechanisms or methods, for example, optical (fluorescence orcolorimetric), magnetic, impedance or conductivity measurement,amperometric, mechanical, etc.

It is to be understood that the present invention will be described interms of a given illustrative architecture for micro-fluidic devices ona substrate or a wafer; however, other architectures, structures,substrate materials and process features and steps may be varied withinthe scope of the present invention.

It will also be understood that when an element such as a layer, regionor substrate is referred to as being “on” or “over” another element, itcan be directly on the other element or intervening elements may also bepresent. In contrast, when an element is referred to as being “directlyon” or “directly over” another element, there are no interveningelements present. It will also be understood that when an element isreferred to as being “connected” or “coupled” to another element, it canbe directly connected or coupled to the other element or interveningelements may be present. In contrast, when an element is referred to asbeing “directly connected” or “directly coupled” to another element,there are no intervening elements present.

A design for an integrated circuit chip may be created in a graphicalcomputer programming language, and stored in a computer storage medium(such as a disk, tape, physical hard drive, or virtual hard drive suchas in a storage access network). If the designer does not fabricatechips or the photolithographic masks used to fabricate chips, thedesigner may transmit the resulting design by physical means (e.g., byproviding a copy of the storage medium storing the design) orelectronically (e.g., through the Internet) to such entities, directlyor indirectly. The stored design is then converted into the appropriateformat (e.g., GDSII) for the fabrication of photolithographic masks,which typically include multiple copies of the chip design in questionthat are to be formed on a wafer. The photolithographic masks areutilized to define areas of the wafer (and/or the layers thereon) to beetched or otherwise processed.

Methods as described herein may be used in the fabrication of integratedcircuit chips. The resulting integrated circuit chips can be distributedby the fabricator in raw wafer form (that is, as a single wafer that hasmultiple unpackaged chips), as a bare die, or in a packaged form. In thelatter case, the chip is mounted in a single chip package (such as aplastic carrier, with leads that are affixed to a motherboard or otherhigher level carrier) or in a multichip package (such as a ceramiccarrier that has either or both surface interconnections or buriedinterconnections). In any case the chip is then integrated with otherchips, discrete circuit elements, and/or other signal processing devicesas part of either (a) an intermediate product, such as a motherboard, or(b) an end product. The end product can be any product that includesintegrated circuit chips, ranging from toys and other low-endapplications to advanced computer products having a display, a keyboardor other input device, and a central processor.

Reference in the specification to “one embodiment” or “an embodiment” ofthe present principles, as well as other variations thereof, means thata particular feature, structure, characteristic, and so forth describedin connection with the embodiment is included in at least one embodimentof the present principles. Thus, the appearances of the phrase “in oneembodiment” or “in an embodiment”, as well any other variations,appearing in various places throughout the specification are notnecessarily all referring to the same embodiment.

It is to be appreciated that the use of any of the following “/”,“and/or”, and “at least one of”, for example, in the cases of “A/B”, “Aand/or B” and “at least one of A and B”, is intended to encompass theselection of the first listed option (A) only, or the selection of thesecond listed option (B) only, or the selection of both options (A andB). As a further example, in the cases of “A, B, and/or C” and “at leastone of A, B, and C”, such phrasing is intended to encompass theselection of the first listed option (A) only, or the selection of thesecond listed option (B) only, or the selection of the third listedoption (C) only, or the selection of the first and the second listedoptions (A and B) only, or the selection of the first and third listedoptions (A and C) only, or the selection of the second and third listedoptions (B and C) only, or the selection of all three options (A and Band C). This may be extended, as readily apparent by one of ordinaryskill in this and related arts, for as many items listed.

Referring now to the drawings in which like numerals represent the sameor similar elements and initially to FIGS. 1A and 1B, a top view (FIG.1A) and a side view (FIG. 1B) are shown of an illustrative particlemanipulation device 10 in accordance with the present principles. Device10 may include a substrate 12 upon which a microfluidic chamber orchannel 30 is formed in a first region or section 18, and second regionsor sections 14 and 16 are configured for including biasing structures 44for producing or radiating energy to bias particles in the channel 30.It should be understood that the second regions 14 and 16 may be formedon any portion of the substrate 12 including to the left of an inlet 32to the right of an outlet 38 below the channel 30 (deeper into or on theother side of the substrate 12, etc.).

The microfluidic channel 30 is configured to receive particles,preferably in solution, and pass through the microchannel 30. During thepassage of the particles through the channel 30, the particles arebiased by the biasing structures 44, which may include, for example,antennae 20, 22. Biasing structures 44 are preferably circuits,transducer elements or other energy or radiation producing elementsconfigured to change the movement of the particles or select a type ofparticles in the microchannel 30. Biasing includes speeding up, slowingdown, changing direction, changing the energy (adding or removingenergy), or any other change imparted to the particles to separate,distinguish or otherwise alter the motion of the particles.

The biasing structures 44 are depicted as antennae 20 and 22 controlledby a voltage and antenna feed control circuit 28. The circuit 28 may beintegrated on the substrate 12 or may be provided externally to thedevice 10. In the example shown in FIG. 1A, the microchannel 30 includesantennae 20 on one side and antennae 22 on the opposite side. Theantennae 20 and 22 are offset along a trap to affect the particlestraveling through the microchannel 30 in different ways. Different typesof radiation may be employed or different operating frequencies,voltages or other characteristic may be employed for operatingstructures 20 and 22. While two types of structures (20 and 22) aredepicted any number of structures and modes or operation may be employedon a same device 10.

In one embodiment, particle or organism trapping (electromagnetictweezers) could be achieved by the combination of the microfluidicchamber 30 and a series of THz antennas 20, 22 or antenna arraysdesigned and powered such that their radiation patterns 24, 26 aredirected towards an observation chamber 34, and they produceconstructive interference at a determined position on the chamber 34where an organism will then be trapped through positivedielectrophoresis (e.g., where the organisms or particles are attractedto electric field maxima). An array of antennas (20, 22) can increasepower and directivity, making the trapping beam narrower and sharper andcreate a more precise trapping spot. Real-time feedback can be achievedusing the control circuit 28, which may include an image sensor such asa cell-phone camera that would capture images and generate theappropriate signal to adjust the amplitude and phase applied to feedeach antenna element and move the trapping spot.

The substrate 12 may include silicon or other semiconductor material,e.g., II-VI, III-V, Ge, etc. The substrate 12 may include glass,ceramic, metal, polymer, organic polymer (e.g., PolyDimethylsiloxane(PDMS), a Si based organic polymer) or any other suitable material. Inone embodiment, the control circuit 28 is integrated in the substrate 12(e.g., silicon or glass) and the structures 44 includeantennae/oscillators 20, 22 within a few mm² chip, which can be poweredby a small battery (not shown) or through a connection to a portabledevice like a cell-phone or tablet which would be used to capture,process the image and produce the necessary signals to control theantenna feed 28. The microfluidic region 18 of the device 10 could befabricated on a Si/Glass/PDMS substrate 12 and can be made detachablefrom the regions 14 and/or 16 holding the antennas 20, 22 such that onlythe microfluidic region 18 is made disposable.

In another embodiment, the microfluidic channel 30 may be formed usingetching processes common to semiconductor processing and the circuits orstructures 44 are integrated with the same substrate 12.

Laser components, optical lenses and filters are not needed to createthe trapping force (although they may be employed and may be used forvisualization in some embodiments).

The biasing structures 44 may take on many forms (e.g., antennae 20, 22,as described). Optimization algorithms in combination with rigorouselectromagnetic solvers can be used to produce antenna designs with thecorresponding amplitudes and phases to feed each antenna element togenerate a desired radiation pattern, with the direction and angularextent, as desired. This optimization can be performed during an antennadesign step. A set of feeding configuration options can bepre-determined during this design step that generates as many radiationpatterns as needed or desired. The various feeding configuration optionswould then be saved in memory of the feed control 28 and be selectedduring device operation to change between radiation patterns or trappingposition or strength.

In addition, some of the antennas 20, 22 can be configured as THz (orother frequency) detectors to extract parameters of the organism orparticle under evaluation in the microfluidic channel or chamber 30based on their scattering characteristics. Further, by designing broadband antennas 20, 22 capable of emitting wide bandwidths of wavelength,spectroscopic analysis of the sample can be performed to identify itsprecise components. Different cells, particles or elements have distinctsignatures in the THz spectra, making THz spectroscopy useful toidentification and imaging. These signatures allow the identification ofmany chemicals through their transmission spectra using THzmultispectral images. THz imagers/detectors need good alignment toradiation, which is not a problem on a chip (substrate 12) where antennaelements 20, 22 are stationary.

By way of example, radiated power density can be defined as: P_(d)=E×H(Watts/m²) or using H=E/h=E/120π: |P_(d)|=EH=E²/120π. Power on anisotropic sphere is: E²/120π=P_(T)/4πr². With E-field amplitudepropagation losses ˜1/r and E-power propagation losses ˜1/r²,

$E = {\sqrt{\frac{120\pi\; P_{T}}{4\pi\; r^{2}} = \frac{\sqrt{30\; P_{T}}}{r}}{\left( {V\text{/}m} \right).}}$For propagation of laser beams r˜100's of cm, and for propagation of THzbeams on a chip, r˜1 mm. Thus, propagation distances of a THz signal ona silicon chip surface can be of the order of 1-2 mm while thepropagation distance of a laser beam on an optical tweezer setup is ofthe order of hundreds of cm's, plus the losses induced by filters andlenses required to focus the beam. Optical tweezers require much morepowerful optical sources (orders of magnitude more power) than thedevice 10 in accordance with the present principles. Further,dielectrophoretic (DEP) force is proportional to the E-field gradient. Avery sharp beam can produce strong DEP forces, E-field absolute strengthis not as important as its sharpness.

In the THz range, the wavelength is of the order of a few hundredmicrons; hence the far field region of radiation is reached within a fewhundred microns to a few mm within the chip or device 10. Operatingwithin the far field region of radiation is preferred to avoid fringefield effects and sidelobes occurring in the near field, at distancesclose to the radiation elements. Hence, when using THz radiation, themicrochannel 30 should be located at a few mm from the antenna radiationto allow for a distance at least 5 times the wavelength, and preferably10 times the wavelength or more. High power THz radiation can achievemaximum powers in the 100's of microW to a few mW. THz radiation oververy short distances can be used for arrays of antennas to radiatehigher power while experiencing small attenuation since the propagationdistances are very short.

Optical tweezers, on the other hand, require the laser light to travellonger distances and through several focusing and filtering elements,which attenuates the radiation power and, therefore requires lightsources with higher power.

Numerous antenna design techniques and design optimization techniquescan be employed to optimize a radiation pattern shape, direction,angular spread, and produce the proper shapes of each antenna radiatingelement and antenna array configuration (including the necessaryamplitude and phase properties of the oscillation feeding each radiationelement such as a patch or a slot antenna), which could be placed at anylocation within the chip 10.

Operating on the THz frequency range is preferred because it can producemore directed, narrower and, therefore sharper radiation patterns. Theoscillator/antenna dimensions may be in the micro-scale and cancompactly integrate arrays of large number of antennas, which canproduce even higher intensities and sharper patterns. For example,millimeter and sub-millimeter (THz) electromagnetic wave radiationoccurs between frequencies 30 GHz and 3 THz with wavelengths from 1 cmdown to 100 microns. Electromagnetic oscillation can be generated mostcompactly through solid state diode sources, which can also be combinedwith multipliers or multiplexers to produce higher frequencies (e.g.,Gunn diodes, GaAs Schottky, IMPATT, etc.). Electromagnetic energy isradiated in the desired direction through antennas 20, 22, includingmicrostrip patch and slot antennas, which are compatible with, e.g.,silicon substrates. Conductors of the antennas 20, 22 may include copperwith a surface finishing of 3 to 5 μm nickel and a few hundrednanometers of gold. Other materials may also be employed.

The antenna design will determine radiation pattern, gain anddirectivity. Smaller dimensions are of interest for portableapplications of dielectrophoresis effects with non-opticalelectromagnetic radiation, achievable with higher frequencies in the THzrange. Smaller antenna and oscillator dimensions can be integrated on achip or device and occupy smaller areas. Smaller antenna size allows forantenna arrays that will enable sharper radiation patterns with higherdirectivity to control micro-particles and higher radiation power.Sharper and more focused radiation patterns are important to producelarger electric field intensity gradients and, therefore larger DEPforces.

A distance between the antenna 20, 22 and the microfluidic channel 30can be multiple times the wavelength (a few hundred microns), whichhelps with directivity since the radiation pattern will be in the farfield or Fraunhoffer region of electromagnetic radiation, thus reducingeffects of sidelobes and other undesired fringe effects characteristicof the near field region of radiation. THz sources may include resonanttunneling diodes (RTDs), which are the highest frequency activesemiconductor devices that can oscillate in the THz range at roomtemperature. RTD oscillators are extremely compact sources of coherentcontinuous wave (CW) THz radiation and just a simple voltage source isneeded to drive them. The THz sources may be integrated with resonatorsformed by slot antennas which help increase efficiency and output power.In other embodiments, Schottky diode-based multipliers may be employedas local oscillators in the submillimeter-wave range due to theircompactness, electronic tunability and stability. These devices candeliver power, e.g., up to 1 mW at 2.5-2.7 THz.

THz photons are nonionizing, meaning they are not energetic enough toknock electrons off atoms and molecules in human tissue, which couldtrigger harmful chemical reactions. THz spectrometers can be used foridentifying chemical composition or medical diagnostics. Recent advancesin THz imaging sensors for medical diagnosis enable the combination ofmanipulation and imaging of organisms or microparticles

DEP force can be provided for a spherical particle that becomespolarized inside a non-uniform electric field E as:F_(DEP)=2π∈_(m)CM*R³∇|E|².

Polarized ions inside a particle can be modeled as a dipole, generatingan electric field superposed to the original field. The polarized beadexperiences a force which is a function of 3 factors: particle radius(R), Clausius-Mossotti factor (CM*) given by the relationCM*=(∈*_(p)−∈*_(m))/(∈*_(p)+2∈*_(m)) between the complex permittivity ofthe particle, ∈*_(p)=∈₀∈_(p)−jσ_(p)/ω, and that of the suspendingmedium, ∈*_(m)=∈₀∈_(m)−jσ_(m)/ω, and the distribution of electric fieldintensity (∇E²). If the electric field surrounding the particle E is aconstant then the DEP force is zero. Only non-uniform electric fieldsproduce non-zero DEP forces. Combinations of DEP force with other forcesaffecting the particle (e.g., diffusion, capillary forces, gravityforces, Brownian motion, etc.) can serve to manipulate (trap, separate,convey, etc.) the particle as determined by the electric fields. Byexploiting the dielectric differences between different particles orcells, DEP techniques can discriminate and sort the particles, forexample, biological cells can be sorted based on differences in membraneproperties (permeability, capacitance and conductivity), internalconductivity, size, etc.

DEP force depends on frequency of oscillation of the electric field. Inlossy media, the complex permittivity of both particle and suspendingmedium are a function of frequency. At low frequencies (ω), conductivity(free charge) or the imaginary component of the complex permittivitydominates, and at high frequencies (ω), the real part of the complexpermittivity dominates. In some examples, for instance a non-conductingbead in non-conducting water, the Clausius-Mossotti term is nearlyconstant with a value of CM*˜−0.5, thus dealing negative DEP across allfrequencies. For a conducting bead in non-conducting water, however, theconductivity dominates at low frequencies giving positive DEP (positiveCM*), but the permittivity dominates at high frequencies, changing tonegative DEP (negative CM*). For a conducting bead in conducting salinesolution, a more complex relation is experienced. DEP force and signdepends on frequency and material properties.

DEP forces may be generated in a plurality of ways. Some of these mayinclude the following. An electromagnetic radiation element on a surfaceof the microfluidic substrate 12 (chip), which is external to themicrochannel 30 to also avoid the challenges associated with the use ofin-situ electrodes in direct contact with the fluid. Electrodes incontact with the fluid channel may also be employed along with otherfeatures. Microstrip patch antennas 20, 22 can be employed asinexpensive electromagnetic radiating elements and can be implemented onthe surface of the substrate 12 with a ground plane 40 on the bottomsurface of the substrate 12 and a coaxial feeding line 48 on the side ofthe chip or through the substrate 12. Antenna configurations andradiation patterns can be optimized to perform any of the trapping,separation or concentration of micro-particles or cells through DEP.Antenna arrays with phased feeds can be employed to further optimize andenhance the directivity of the radiation beam or to allow real-time beamsteering through control circuitry and semi-independent feeding ofantennas, providing flexibility to change the DEP functionality inreal-time.

Other elements for focusing biasing structures 44 may includeelectromagnetic band-gap structures, metamaterial components, surfaceplasmon inducing elements, acoustic energy producing elements (e.g.,piezoelectric transducers), optical antennas or nanoantennas,electrodeless DEP elements, etc. Alternatively, the electromagneticradiation element or biasing element 44 can be implemented externally tothe microfluidic chip as part of a detection/controlling circuitry thatis not necessarily in direct contact with the chip substrate. In-situelectrodes 47 may be employed inside or adjacent to the microchannel 30and be used for more advanced functionality.

An in-situ image sensor array component 46 (e.g., CMOS or CCD based) maybe integrated into the device 10 or as part of an external reader andcontrolling circuitry to capture real time images of the flow throughthe microchannel(s) 30. The image sensor 46 can be connected with animage processing element 50 that determines the status of the fluid flowin the channel 30 and determines the proper feedback signal to beapplied on the antenna feeding line 48 to produce the optimum radiationpattern through a feedback control loop for real-time particlemanipulation. In one embodiment, the image sensor 46 and the imageprocessing element 50 can be used for detection for more accurate andprecise diagnostic purposes.

The image processing element 50 may be integrated on the substrate 12 ormay be connected externally. The image processing element 50 may includesoftware for image pattern recognition or other image processing. In oneembodiment, the image processing element 50 may be employed to analyzecells, e.g., to separate parasitized malaria cells versus healthy cells,for sorting and concentration through electromagnetic-based DEP andimage capture and identification with image pattern recognition softwareon image processing element 50. Image processing element 50 may beintegrated on the substrate 12 or be an external module.

Referring to FIG. 1B, the device 10 shows a microchannel or chamber 30etched or otherwise formed in the substrate 12. This embodiment depictselectrodes (antenna) 22 formed on an insulating layer 42 which may be ator near a surface of the microchannel 30. Other layers 45 may be formedabove or below the insulating layer 42.

Referring to FIG. 2, another device 110 includes a combination of amicrofluidic chamber 130 and a series of THz antennas or antenna arrays120 designed and powered in a way that their radiation patterns aredirected towards an observation chamber 134 and they produceconstructive interference at a determined position on the chamber 134where an organism 135 will then be trapped through positivedielectrophoresis (where the organisms or particles are attracted toelectric field maxima). The array of antennas 120 can increase power anddirectivity, making the trapping beam narrower and sharper and create amore precise trapping spot. Real time feedback can be achieved by theuse of a simple image sensor such as a camera 140 on a cell-phone 142 orother external device. The camera captures images 144 and generates anappropriate signal on a feedback loop 146 to adjust the amplitude andphase applied to feed each antenna element 120 and move the trappingspot.

Referring to FIG. 3, in another embodiment, another device 200 includesa microfluidic channel 230 with a more complex structure having multiplechambers and paths formed on a substrate 201 (chip). The device 200includes an electromagnetic radiation or biasing structure 202, whichcan be designed to perform several consecutive steps of a test orprocedure on a single chip. The device is depicted at two instancesduring its operation.

In a first instance 210, a test may require that two or more fluids 222,224 need to be mixed with a sample introduced at a sample inlet 232 (orone fluid used to rinse a target microorganism or particle from theother containing fluid). This organism travels down a channel 235 and isretained in a mixing chamber 234 through positive dielectrophoresisapplied through an antenna array 204 that produces a radiation pattern205 directed to the mixing chamber 234. The mixing chamber 234 isconnected through another microchannel 236 to a second inlet 238 where areacting substance (or rinsing substance) 224 is inserted, intended tobe mixed with the target organism.

The antenna array 204 is connected to a small voltage generator 240(with a small battery or via a mobile device attachment) and somecircuitry to control the antenna feed (amplitudes and phases) such thatthe microorganisms or particles are trapped at the proper time (t=t₁).

In a second instance 220, the antenna array 204 is deactivated and anantenna array 202 is activated using generator 240 and some circuitry tocontrol the antenna feed (amplitudes and phases). The first mixingchamber 234 is connected through another microchannel 237 to a secondmixing chamber 242, which is also connected through microchannel 244 toa third inlet 252. Fluid 254 is introduced into a fluid inlet 252 tofurther rinse (or to insert a reacting substance to be mixed with) thespecimens in the second mixing chamber 242. The antenna array 202 may beemployed to trap and retain a different organism in chamber 242 for theduration of the rinsing (or reaction) step using radiation 207 inducedDEP forces. The microchamber 242 is connected through a microchannel 246with the outlet 250 for the retrieval of the reacted and rinsedmicroorganisms or elimination of unnecessary fluid. The microorganismsor particles trapped in microchamber 242 through radiation 207 arereleased to be allowed to move to the outlet 250 at the proper time(t=t₁+Δt) by turning off the radiation 207.

Referring to FIG. 4, in another embodiment, another device 300 includesa microfluidic channel 330 with a more complex structure having multiplechambers and paths. The device 300 includes an electromagnetic radiationor biasing structure 344 that is designed along with the microfluidicchannel 330 to separate particles of different size or compositionthrough dielectrophoresis (e.g., negative DEP (neg-DEP) where theorganisms or particles are repelled from electric field maxima). Theneg-DEP force depends on the particle size (R³) and composition (throughits dielectric constant), hence particles of different sizes and/orcomposition can be separated by generating electric field patterns ofvarying strength. In this example, there are three channels 346, 348 and350 configured to separate particles or cells 358, 360 and 362 intochambers or outlets 352, 354 and 356.

By creating side channels 346 and 350 from the main microchannel 348towards which the different particles 358, 360 and 362 can be guided, amix of particles 358, 360 and 362 can be separated by directing eachtype towards one of the side channels 346 and 350 or allowing theparticles 360 to pass unaffected to chamber 354. Different radiationpatterns 324 and 326 from various sets of biasing structures 344 such asantenna arrays 320 and 322 can be optimized to produce the necessaryelectric field strength at the corresponding channel bifurcations.

In one illustrative embodiment, a fluid 314 including particles 358, 360and 362 is introduced at inlet 332 and flows through a path 336 to aseparation chamber 334. Particles 358 are most sensitive to DEP force.This type of bead is repelled by the first electromagnetic beam 324created by a first set of antennas 320 and moved towards the first sidechannel 346. Particles 362 are passed unaffected through the first DEPinducing beam 324 because the force strength was not stronger than thefluid drag. This could be due to the particle size not being largeenough. This particle type (362) however is affected by the beam 326produced by a second set of antennas 322 producing a stronger DEP force,and being directed towards the second side channel 350. Particles 360pass unaffected through both DEP induced beams 324, 326, possibly due toa small size that makes the DEP force much weaker than the drag force ofthe fluid. The paths 350, 348 and 346 can branch off from a separationchamber 334 at different locations or may be disposed in otherorientations as needed.

As before, the antennae 320 and 322 are controlled using a voltage andfeed control circuit 328. Circuit 328 may be integrated into the chip ordevice 310 or may be connected externally. In one embodiment, differentcircuits 328 may be interchangeably connected to the chip 310 to providedifferent functions or controls to the biasing structures 344. Inanother embodiment, the circuit 328 may provide controls for adjustingthe voltage, phase and other characteristics of the biasing structures344 for controlling the timing, power, radiation (shape), etc. a priorior in real-time. The controls may be based on feedback, such as visualfeedback (image sensors or other sensors, e.g., temperature, flow,etc.).

Referring to FIG. 5, another device 400 includes a chip 410 having acombination of a microfluidic chamber 430, a number of biasingstructures 444 and 446 and a detection sensor 448. The device 400 willbe illustratively described in terms of performing a test for red bloodcells infected by malaria.

It is known that healthy red blood cells retain ions inside the cellsand present a higher conductivity, leading to a positive-DEP response.The outer membrane of infected red blood cells, on the other hand, iscompromised and unable to retain ions inside the cell, hence presentinglow conductivity and a negative-DEP response. This means that healthyblood cells will be trapped by high intensity E-fields while infectedblood cells will be repelled by high intensity E-fields. This differencein behavior can be used to separate healthy from infected red bloodcells within microfluidic channels 436 and 440.

The testing device 400 includes a staining or rinsing chamber 434, wherethe fluid for staining or rinsing of the red blood cells can be mixedwith the sample, to either help with later visualization (when opticaldetection or diagnosis is used, either manual or computerized) or toeliminate spurious elements in the sample that could compromise themeasurement that can be performed inside the observation chamber 442.For example, the rinsing fluid can be inserted from a rinsing inlet 426into the mixing or rinsing chamber 434 that also receives a sample fluid462 containing the red blood cells (healthy and infected) from an inletchamber 432.

Biasing structures 444 may include a set of antennas designed andlocated such that a radiation pattern 424 is directed towards the mixingor rinsing chamber 434 so that both healthy cells and infected cells aretrapped inside the chamber 434. Healthy cells will be trapped within theradiation pattern maxima while unhealthy cells will be prevented frommoving forward because they are repelled by the radiation patternmaxima.

This rinsing chamber 434 is connected to a second microchannel 428 thatcommunicates with the inlet 426 where the rinsing or staining fluid isinserted into the chip 410 and flows toward the rinsing chamber 434where red blood cells are being retained. Unhealthy cells cannot flowtowards this secondary channel 428 because the fluid is flowing in theopposite direction, that is, towards the chamber 434.

The antenna arrays 444, 446 within the chip 410 are connected to avoltage generator circuit 458 or a battery controlled by a feedbacksystem that turns the array on and off for a predetermined time.

A second step in the test performed in the microfluidic channel 430separates the healthy from infected red blood cells taking advantage ofthe different DEP responses exhibited by each of these types of cells.Infected cells are rejected from a high intensity E-field and can beguided towards a separate channel 440 towards a final observationchamber 442. Similarly, the antenna array 446 produces a necessaryelectric field pattern 425 and is connected to the voltage generator 458and controlled through feedback circuitry that determines timing.

The infected cells are guided towards the observation chamber 442 wheredetection will be carried out by a sensor 448 in one of several possiblemethods. For example, optical detection may be performed using an imagesensor (448) focused on the observation chamber 442 with a transparenttop cover. Another option may include using another set of THz antennas(448) to perform detection of scattered waves 427 from the contentsinside the observation chamber 442 to determine its composition. THzspectroscopic analysis can provide precise identification of the samplecomposition and can thus produce not only a diagnosis but even identifythe strain and degree of the infection. Other sensors 448 may also beemployed. The radiation pattern 425 generated by the antenna array 446can be designed to be of an intensity lower to that of radiation pattern424 generated by the antenna array 444 so that the DEP force produced isnot enough to overcome the hydrodynamic drag force and, thereforehealthy cells flow through the separation chamber 436 unaffected to anoutlet chamber 438.

For an accurate diagnosis, the detection sensor 448 produces a signal(from the optical or THz sensor) that is to be processed and contrastedagainst a database, through the use of a program stored in a signalprocessing unit 460 connected or integrated on the chip 410.

Variations of the device 400 can be envisioned to perform other tests orexperiments. For example, an immunoassay test can be performed to detectdiseases such as e-Coli or the common flu by the use of functionalizedmicro-particles or beads with antibodies that are mixed with the sample(blood or other fluids) within a vial and then inserted into themicrochannel 430 through the inlet 432. The beads can then be trappedwithin a chamber (e.g., 434) with an antenna array 444 radiation pattern424 directed towards the chamber exit that prevents the beads fromcontinuing through microchannel 430. The secondary inlet 426 andmicrochannel 428 connected to the same trapping chamber 434 are employedto insert labeled (e.g., magnetic, colorimetric, fluorescent) antibodiesand allowed to mix for some time with the trapped functionalized beadsin chamber 434. The beads can then be allowed to proceed through channel436 and guided with negative DEP towards the observation chamber 442 fordetection. Another rinsing step can also be included. Detection can beperformed by using THz detection with the corresponding signalprocessing software. Alternatively, optical or magnetic detection arealso contemplated.

Referring to FIG. 6, a device 500 is illustratively shown. The device500 may be employed for field testing or may be incorporated into apoint or care (PoC) device. Applications may include water testing,blood testing, quality testing in factory environments, etc. The device500 includes a chip 510 having a microfluidic channel 530, biasingstructures 520 and a detection sensor 522. For illustration purposes,chip 510 may be considered to be similar to device 400. The biasingstructures 520 may include different types of structures and provideddifferent types of radiation or energy. Similarly, the detection sensor522 may be an image sensor, or may include another set of THz antennasto perform detection of the scattered waves, or can comprise other typesof detection mechanisms (e.g., magnetic, impedimetric, etc.). Thebiasing structures 520 and detection sensor 522 are provided on asubstrate 512. The channel 530 may be formed on the substrate 512 or maybe formed on a separate substrate 516 so that it can be removed anddisposed of. In other embodiments, the entire chip 510 may bedisposable. The microfluidic channel 530 can be fabricated in a way thatcan be inserted into the substrate 512, which includes the biasingstructures 520, detection sensor 522 inside a larger device housing(with biasing elements non-disposable). Alternatively, all components ofthe “microfluidic and radiation chip 510 can be integrated into a samesubstrate for a one-time use and be made disposable.

The device 510 includes an electrical contact portion 524 configured toconnect with the biasing structures 520 and detection sensor 522 tocontrol the biasing structures 520 and control and collect data from thedetection sensor 522 and any other devices or components on the chip510. An electrical connector 525 detachably connects to the electricalcontact portion 524 of the chip 510 and may include a ribbon or othercable 526 to interface with a reader device 550.

The reader device 550 may include a specially designed device or mayemploy the functionality of an existing device, such as, e.g., a smartphone, computer or other computing device configured to interface withand control the chip 510. The reader device 550 may include a portableenergy source 552 although other energy sources may be employed (e.g.,outlet power, solar power, etc.). The reader device 550 includes aprocessor or microcontroller 558. The microcontroller 558 includesmemory for storing programs, protocols and/or control features. In oneembodiment, a voltage signal generator 554 is controlled by themicrocontroller 558 to provide power signals to the biasing structures520 on the chip 510. A detector or sensor interface 556 is included tocontrol and receive feedback from the detection sensor 522, such asimages or sensed parameters to provide for adjustments in the voltagesignals from the voltage signal generator 554 as processed by themicrocontroller 558.

The reader device 550 may include other features such as a displayinterface 560 for displaying images or connecting to a display forrendering images or other information. A communications interface 562may be included for communicating with other devices or networks. Forexample, the interface 562 may provide Bluetooth® or othercommunications links for downloading or uploading information orprograms as needed. The reader device 550 may be a modular, portableelement, that is, a separate reader or a smart-phone attachment. Thereader element may include additional electronic modules or softwareapplications with various functions.

Referring to FIG. 7, a device 600 is illustratively shown. The device600 may be employed for field testing or may be incorporated into a PoCdevice. Applications may include water testing, blood testing, qualitytesting in factory environments, etc. The device 600 includes a chip 610having a microfluidic channel 630, biasing structures 620 and detectionsensor 622. The biasing structures 620 may include different types ofstructures and provide different types of radiation or energy.Similarly, the detection sensor 622 may be an image sensor, or mayinclude another set of THz antennas to perform detection of thescattered waves, or can comprise other types of detection mechanism(e.g., magnetic, impedimetric, etc.). The biasing structures 620 anddetection sensor 622 are provided on a substrate 612. The channel 630may be formed on the substrate 612 or may be formed on a separatesubstrate 616 so that it can be removed and disposed of.

The device 600 may be monolithic including all microfluidic, radiationand electronic elements in a single non-disposable chip. The electronicmodules may include a voltage signal generator 654 (similar to generator554, FIG. 6) to feed the biasing structures/elements 620 with varyingamplitude and phase to create the appropriate radiation patterns. Adetector interface and signal conditioning unit 656, similar to theinterface 556 (FIG. 6) are provided. The appropriate detection sensingelement 622 is included for optical, magnetic or other energy/radiationmechanism. If using THz imaging for detection, then a THz detector andits interface are provided. A microcontroller and memory 658 areincluded to execute programs, generate command signals and store theprograms and results. A display unit or interface 660 may be included toshow results to a user in real-time. A communications unit or interface662 may be included with, e.g., a Bluetooth® or other wireless or wiredcommunication interface such that the results can be transmitted to acellphone, a computer, a remote database, etc. A battery 652 or otherpower source may be included to power the device 600.

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems), and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer readable program instructions.

These computer readable program instructions may be provided to aprocessor of a general purpose computer, special purpose computer, orother programmable data processing apparatus to produce a machine, suchthat the instructions, which execute via the processor of the computeror other programmable data processing apparatus, create means forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks. These computer readable program instructionsmay also be stored in a computer readable storage medium that can directa computer, a programmable data processing apparatus, and/or otherdevices to function in a particular manner, such that the computerreadable storage medium having instructions stored therein comprises anarticle of manufacture including instructions which implement aspects ofthe function/act specified in the flowchart and/or block diagram blockor blocks.

The computer readable program instructions may also be loaded onto acomputer, other programmable data processing apparatus, or other deviceto cause a series of operational steps to be performed on the computer,other programmable apparatus or other device to produce a computerimplemented process, such that the instructions which execute on thecomputer, other programmable apparatus, or other device implement thefunctions/acts specified in the flowchart and/or block diagram block orblocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods, and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof instructions, which comprises one or more executable instructions forimplementing the specified logical function(s). In some alternativeimplementations, the functions noted in the block may occur out of theorder noted in the figures. For example, two blocks shown in successionmay, in fact, be executed substantially concurrently, or the blocks maysometimes be executed in the reverse order, depending upon thefunctionality involved. It will also be noted that each block of theblock diagrams and/or flowchart illustration, and combinations of blocksin the block diagrams and/or flowchart illustration, can be implementedby special purpose hardware-based systems that perform the specifiedfunctions or acts or carry out combinations of special purpose hardwareand computer instructions.

Referring to FIG. 8, methods for particle manipulation areillustratively shown in accordance with the present principles. In block802, a fluid having particles therein is introduced to a microchannel.The microchannel is included in a substrate and configured to receivethe fluid having the particles therein. The microchannel may include oneor more paths, traps, chambers configured to trap, separate or redirectparticles biased by biasing structures.

In block 804, the particles traveling in the microchannel are biasedusing at least one biasing structure formed on the substrate adjacent tobut outside the microchannel. The at least one biasing structure isconfigured to dispense radiation at a frequency to bias movement of theparticles within the microchannel from outside the microchannel. In oneembodiment, the biasing structure includes at least one antenna.

In block 806, radiation is generated to apply dielectrophoresis forcesto the particles. The biasing structure or structures may be placedadjacent to the microchannel in a number of positions corresponding tochambers or pathways. The biasing structures are controlled by adjustingtheir power, phase or other characteristics. The biasing structures maybe synchronized to perform different tasks while the particles movethrough the microchannel. For example, a first biasing structure maytrap particles for observation, rinsing or other steps and a secondbiasing structure may separate particles of a certain type. Theparticles may be inorganic compositions, organic compositions,combinations of inorganic and organic materials, cells or otherparticulate matter.

The biasing structure(s) generate radiation to apply dielectrophoresisforces to the particles based on system feedback (visual feedback,sensor feedback, characteristics, etc.). The radiation may include oneor more of terahertz range electromagnetic radiation, or include or becombined with acoustic energy transducers (e.g., piezoelectricmaterials) to generate acoustic waves, or include or be combined withmagnetic field sources. Other types of energy and different frequencyranges may also be employed in accordance with the present principles.

In block 808, particles may be detected or analyzed using a sensorconfigured to detect characteristics of the particles. Thecharacteristics may include motion of the particles, absorption spectra,fluorescence emission, magnetic properties, density, quantity, color,shape, and any other characteristic. The sensor may include an antenna,an image sensor, etc.

In block 810, the microchannel may be separable from the substrate, andmay be disposed of after use. In one embodiment, the microchannel andthe biasing structures are integrated on a same chip and the chip may bemade disposable.

It should be understood that the present principles may be employed forfield testing of cells, particulates in fluids, etc. In usefulembodiments, the devices described here may be employed in Point of Careapplications and may be used to determine or evaluate a number ofdiseases or conditions. In some embodiments, the microchannels wherebodily fluid or contaminated fluids are placed can be disposable withoutdisposing of the remaining structures of the device. It should also beunderstood that the components of the devices described herein may becombined in any combination to provide desired functionality.

Having described preferred embodiments for devices for trapping andcontrolling of microparticles with radiation (which are intended to beillustrative and not limiting), it is noted that modifications andvariations can be made by persons skilled in the art in light of theabove teachings. It is therefore to be understood that changes may bemade in the particular embodiments disclosed which are within the scopeof the invention as outlined by the appended claims. Having thusdescribed aspects of the invention, with the details and particularityrequired by the patent laws, what is claimed and desired protected byLetters Patent is set forth in the appended claims.

What is claimed is:
 1. A particle manipulation device, comprising: asubstrate; a microchannel included in the substrate and configured toreceive a fluid including particles therein; and at least one biasingstructure comprising an antenna formed on the substrate adjacent to butoutside the microchannel, the at least one biasing structure configuredto generate radiation at a frequency to bias movement of the particleswithin the microchannel from outside the microchannel.
 2. The device asrecited in claim 1, wherein the microchannel includes a plurality ofpaths configured to separate particles biased by the biasing structures.3. The device as recited in claim 1, wherein the microchannel includesat least one chamber for trapping particles biased by the biasingstructures.
 4. The device as recited in claim 1, wherein themicrochannel includes at least one chamber for detecting particles, andthe device further comprises an image sensor configured to detectcharacteristics of the particles in the at least one chamber.
 5. Thedevice as recited in claim 1, wherein the microchannel is integrated ina removable region that is separable from the substrate.
 6. The deviceas recited in claim 1, wherein the at least one biasing structureincludes at least one solid state diode source configured to use thegenerated radiation to apply dielectrophoresis forces to the particles.7. The device as recited in claim 1, wherein the at least one biasingstructure generates radiation to apply dielectrophoresis forces to theparticles such that the particles are located in a far field region ofthe radiation.
 8. A particle manipulation device, comprising: a chipincluding: a substrate; a microchannel included in the substrate andconfigured to receive a fluid including particles therein; at least onebiasing structure comprising an antenna formed on the substrate adjacentto but outside the microchannel, the at least one biasing structureconfigured to generate radiation at a frequency to bias movement of theparticles within the microchannel from outside the microchannel; and acontrol module including: a generation circuit configured to generate asignal for exciting the biasing structures.
 9. The device as recited inclaim 8, wherein the microchannel includes one or more of: a pluralityof paths configured to separate particles biased by the biasingstructures; at least one chamber for trapping particles biased by thebiasing structures; or at least one chamber for detecting particles. 10.The device as recited in claim 8, wherein the control module and thechip are integrated on the substrate.
 11. The device as recited in claim8, wherein the control module and the chip are integrated together on amonolithic substrate.
 12. The device as recited in claim 8, wherein thechip includes a detection structure integrated on the substrate andcontrol module includes a detector interface for providing feedback toadjust the at least one biasing structure.
 13. The device as recited inclaim 12, wherein the detection structure includes at least one antennaconfigured to detect characteristics of particles in the microchannel.14. The device as recited in claim 8, wherein the at least one biasingstructure includes at least one solid state diode source configured togenerate radiation to apply dielectrophoresis forces to the particles.15. The device as recited in claim 8, wherein the at least one biasingstructure generates radiation to apply dielectrophoresis forces to theparticles such that the particles are located in a far field region ofthe radiation.
 16. A method for particle manipulation, comprising:introducing a fluid having particles therein to a microchannel includedin a substrate and configured to receive the fluid having the particlestherein; and biasing the particles traveling in the microchannel usingat least one biasing structure comprising an antenna formed on thesubstrate adjacent to but outside the microchannel, the at least onebiasing structure being configured to generate radiation at a frequencyto bias movement of the particles within the microchannel from outsidethe microchannel.
 17. The method as recited in claim 16, wherein themicrochannel includes one or more paths and chamber configured to trap,separate or redirect particles biased by the biasing structures.
 18. Themethod as recited in claim 16, further comprising detecting particlesusing a sensor configured to detect characteristics of the particles.19. The method as recited in claim 16, wherein the microchannel isseparable from the substrate, and the method further comprisingdisposing of the microchannel after use.
 20. The method as recited inclaim 16, wherein the at least one biasing structure includes at leastone solid state diode source, the method further comprising generatingradiation to apply dielectrophoresis forces to the particles.
 21. Themethod as recited in claim 16, wherein the at least one biasingstructure generates radiation to apply dielectrophoresis forces to theparticles such that the particles are located in a far field region ofthe radiation.
 22. The device as recited in claim 3, wherein the biasingstructures are configured to trap the particle in a position within theat least one chamber.
 23. The method as recited in claim 17, wherein thebiasing structures are configured to trap the particle in a positionwithin the one or more paths and chamber.
 24. The device as recited inclaim 1, wherein the antenna comprises a resonant tunneling diode. 25.The device as recited in claim 8, wherein the antenna comprises aresonant tunneling diode.